The proposed research will test the hypothesis that survival of developing neurons in the central nervous system depends on: 1) access to trophic substances contained within connecting neuronal populations; and 2) the appropriate balance of synaptic connections among these populations. An in vivo assay system, combining neural transplantation and tissue culture techniques, has been developed to test for the existence of target derived trophic factors which promote neuron survival in the developing rat visual system. Posterior cortical tissue from fetal rats is transplanted into infant rats with cortical lesions in order to rescue temporarily thalamic neurons which would normally die rapidly after the lesions. Strategies are proposed to enhance and prolong this neuron rescue, and to identify the most potent sources of trophic support. Other experiments will test the specificity of the trophic influences and whether the effect is mediated by diffusable or transported substances derived from transplanted neurons. It is suggested that once a neuron has achieved this initial trophic support, it must gain an appropriate numerical balance of afferent and target contacts. Quantitative electron microscopic methods will be applied to retinal ganglion cells in experimental situations where this balance is upset. Th experiments will show whether these neurons adjust their connectivity to restore the balance. Both developing and regenerating cell populations will be tested, to determine if adult regenerating neurons retain this requirement for balanced connections. An understanding of the specific requirements of CNS neurons for survival is essential for developing therapies to maintain or restore neuronal populations in conditions of abnormal brain development.